Clinical Research Directory

Rezvilutamide With Radical Prostatectomy and Metastasis-Directed Therapy in Oligometastatic Prostate Cancer

Prostate cancer represents the second most common malignancy in men worldwide. Oligometastatic prostate cancer (OMPC), defined as a transitional state between localized and widespread metastatic disease (≤10 metastatic lesions without visceral metastases), exhibits relatively indolent biological behavior, offering a window for curative-intent multimodal therapy. While standard systemic therapy with androgen deprivation therapy (ADT) plus novel hormonal agents (NHA) remains the backbone for metastatic hormone-sensitive prostate cancer (mHSPC), emerging evidence suggests that maximal cytoreductive therapy-combining systemic treatment with local interventions (Radical prostatectomy（RP） and Metastasis-directed radiotherapy（MDT）)-may improve survival outcomes. Rezvilutamide (SHR3680), a novel androgen receptor inhibitor independently developed by a Chinese pharmaceutical company, has demonstrated superior radiographic progression-free survival (rPFS) and overall survival (OS) compared to bicalutamide in high-volume mHSPC (CHART study). However, the value of adding metastasis-directed radiotherapy (MDRT) to rezvilutamide and radical prostatectomy in OMPC remains unproven. This trial hypothesizes that maximal cytoreductive therapy (systemic therapy + surgery + MDRT) will significantly prolong progression-free survival (PFS) compared to systemic therapy alone. This is a multicenter, three-arm, open-label, randomized controlled phase II clinical trial (Protocol No.: MA-PCa-II-023; Lead Investigator: Prof. Bo Dai, Fudan University Shanghai Cancer Center). The study will enroll 300 patients randomized in a 2:2:1 ratio to: Arm A (Experimental): Rezvilutamide (240 mg QD) + ADT → radical prostatectomy at month 3 (if PSA decline ≥50%, castrate testosterone level, and resectable disease) → MDT (SBRT 30-40 Gy/3-5 fractions) to all evaluable metastases at month 6 （ 3 month post-surgery） Arm B (Control): Rezvilutamide (240 mg QD) + ADT alone Arm C (Factorial): Rezvilutamide (240 mg QD) + ADT → radical prostatectomy at month 3 (without MDT) Eligible patients are males ≥18 years with histologically confirmed prostate adenocarcinoma (no neuroendocrine differentiation), newly diagnosed mHSPC with oligometastatic disease (≤10 bone/lymph node metastases on conventional imaging; no visceral metastases), and planned ADT. Key exclusion criteria include prior radical prostatectomy, pelvic radiotherapy, systemic therapy for prostate cancer (except ≤4 weeks of ADT), or contraindications to surgery/radiotherapy. The primary endpoint is PFS, defined as time from randomization to first biochemical progression (PSA rise ≥25% and ≥1 ng/mL above nadir confirmed after ≥3 weeks), radiographic progression (RECIST 1.1/PCWG4), clinical progression (new symptoms from local/metastatic disease), or death. Secondary endpoints include rPFS, OS, PSA response rates (PSA50/PSA90), local therapy completion rate, time to CRPC, quality of life (FACT-P and EPIC-26 questionnaires), and safety profiles. Exploratory endpoints evaluate the role of baseline PSMA PET/CT in staging and the development of artificial intelligence models using multimodal data (clinical, imaging, pathology, molecular) to predict prognosis.

5500/20 vs. SABR or Brachytherapy for PRimary OligoMetastatic Prostate Cancer Treatment (PROMPT)

We will investigate whether ultrahypofractionation using stereotactic ablative radiotherapy (SABR) or brachytherapy is as well-tolerated as moderately hypofractionated external beam radiotherapy (EBRT) for treating the prostate in patients with oligometastatic prostate cancer. Secondary aims include assessment of progression-free survival (PFS) and overall survival (OS) as well as cost-effectiveness. We hypothesize that ultrahypofractionation will maintain favorable toxicity profiles and quality of life while achieving comparable or better efficacy, thereby providing a convenient and cost-effective alternative to moderately hypofractionated EBRT.

Comprehensive Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer

This study is a multicenter, randomized controlled phase III clinical trial (PROLONG-3) designed to evaluate the survival benefit of comprehensive radiotherapy combined with primary tumor radiotherapy versus primary tumor radiotherapy alone in patients with newly diagnosed oligometastatic prostate cancer. The trial enrolled 390 patients with ≤10 metastatic lesions confirmed by PSMA PET imaging, who were randomized in a 2:1 ratio to either the intervention group (comprehensive radiotherapy + standard systemic therapy) or control group (primary radiotherapy + standard systemic therapy). Stratification factors included Gleason score (GS ≤8 vs. GS 9-10) and number of metastases (1-3 vs. 4-10). The primary endpoint was 3-year progression-free survival (PFS), with secondary endpoints encompassing overall survival (OS), intermittent treatment rate, adverse events (CTCAE v5.0), and quality of life (EORTC QLQ questionnaires). To minimize bias, stratified block randomization and blinded endpoint adjudication were implemented, with treatment effects analyzed using Kaplan-Meier survival curves and Cox proportional hazards models. The study's innovation lies in its definitive evaluation of the added value of comprehensive radiotherapy, combined with exploratory biomarker analyses (including genomic testing) to identify predictive markers of therapeutic response. Should the results demonstrate significant PFS improvement with comprehensive radiotherapy, this would provide high-level evidence to guide clinical practice, potentially influencing treatment guideline updates while optimizing patient quality of life and reducing healthcare burdens.

Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy

The aim of this study is to assess the progression free survival (PFS) of SABR alone and SABR + 177Lu-prostate-specific membrane antigen (PSMA) in patients with oligometastatic prostate cancer undergoing PSMA positron emission tomography (PET) staging.

Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer

This study will evaluate the safety and effectiveness of a combination of study drugs including zimberelimab, etrumadenant, and quemliclustat in combination with metastasis-directed irradiation in men with hormone sensitive oligometastatic prostate cancer. The study aims to test the hypothesis that targeted inhibition of the adenosine signaling axis (quemliclustat (CD73 antagonist) + etrumadenant (A2AR/A2BR antagonist)) and immune checkpoint inhibition (zimberelimab, α-PD-1) in combination with metastasis-directed stereotactic body radiation therapy (SBRT) will improve local control, progression-free survival (PFS), and hormone therapy-free survival and mitigate immunosuppressive changes to the tumor microenvironment (TME), compared to SBRT alone.

Maximal Tumor Eradication for Oligometastatic Prostate Cancer

In China, the incidence of prostate cancer is increasing in recent years, and it has ranked 5th among common male tumors and 1st in urinary tumors. Unlike developed countries in Europe and the United States, in China, because prostate-specific antigen (PSA) screening has not been widely popularized, and early prostate cancer is mostly asymptomatic, about 13%-26% of prostate cancer patients have progressed to metastatic hormone-sensitive prostate cancer (mHSPC) at the time of initial diagnosis. Compared with localized prostate cancer, the 5-year survival rate of mHSPC is only 29.3%, which is prone to symptoms such as bone pain, pathological fracture, hematuria, and dysuria and seriously decrease the survival and quality of life. As a result, it is of great significance to carry out more refined management of mHSPC, explore more scientific treatment options, and delay the time to CRPC, which is of great significance for improving the prognosis and quality of life of patients and reducing medical burden. However, there is still no standard treatment strategy for OMPC patients which need more clinical exploration. Treatment of prostate primary in oligometastatic prostate cancer (OMPC) may improve survival and do not significantly increase complications. Radiotherapy showed excellent therapeutic effects on metastatic lesions, prolonged survival and without increasing significant adverse effects. In 2019, The New England Journal of Medicine reported a TITAN study that combining apatamide with ADT for metastatic hormone-sensitive prostate cancer, which significantly reduced the risk of death (82.4% VS 72.5%, P=0.005), and improved progression-free survival (68.2% VS 47.5, P \<0.001) without increasing adverse effects of treatment. In 2020, Johns Hopkins University published a phase I clinical study of radical treatment of 12 cases of OMPC. Patients were treated with neoadjuvant docetaxel chemotherapy or abiraterone, combined with radical prostatectomy for primary lesions, and stereotactic radiation for bone metastases to achieve the purpose of complete tumor eradication. Preliminary results showed that no additional complications were found except neutropenic fever in two cases. At the same time, the proportion of PSA maintained undetectable in 1,2,3 years was 12 / 12 (100%), 10 / 12 (83%) and 8 / 12 (67%), respectively, showing good treatment results. Since 2014, the applicant has rich research experience in the treatment of oligometastatic prostate cancer and our results showed that systemic therapy combined with local tumor reduction therapy can confer a survival benefit for OMPC patients without a significant increase in complications. This clinical trial aimed to analyze the clinical efficacy and safety of maximal tumor eradication strategy for oligometastatic prostate cancer.

Genomic Biomarker-guided Neoadjuvant Therapy for Prostate Cancer (SEGNO)

To evaluated the safety and efficacy of genomic biomarker-guided neoadjuvant therapy for locally advanced and oligometastatic prostate cancer.

Prostate Oligometastatic Cancer Management Driven by Disease Biology et/or Immunoactivity (PROMETEO)

Currently, despite the advent of next-generation imaging has improved the detection of Oligometastatic prostate cancer (OMPC), prognostic biomarkers able to stratify patients and monitor treatment response are lacking and urgently needed. Mounting evidence suggests that molecular profiling of the disease and host immune activity evaluation can reveal OMPC heterogeneity and address the above unmet clinical need. This study aims at combining the analysis of several biomarkers to improve the prognostic stratification of OMPC patients